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Junchao Chen, Clara Oromendia, Joshua A Halpern, Karla V Ballman
PURPOSE: Recent years have brought many changes in the management of localized prostate cancer as national screening guidelines have been updated and diagnostic practice patterns evolved. We sought to better understand how the changing landscape influenced treatment utilization in the United States. METHODS: We used the SEER database in this retrospective analysis of patients with clinically localized prostate cancer between 2004 and 2013. We evaluated utilization of primary treatment modalities over time with descriptive and trend analyses, and examined treatment utilization by cancer risk group and age at diagnosis...
March 14, 2018: Prostate
Yao Wang, Haitao Xu, Lihui Si, Qiuju Li, Xiujie Zhu, Tong Yu, Xiaokun Gang
BACKGROUND: Our study was aimed at detecting the expression levels of miR-206 in prostate cancer (PCa) tissues and PCa cell lines, and exploring the potential functions of miR-206 by targeting chemokine ligand 11 (CXCL11). METHODS: RT-qPCR was applied to detect the expressions of miR-206 and CXCL11 in PCa tissues and in PCa cell lines. Expression of the CXCL11 protein was detected using Western blot. After manipulating the expression of miR-206 and CXCL11 in PC-3 and DU-145 cells, the changes of cell proliferation and cell cycle were observed through cell counting kit-8 (CCK-8) and flow cytometry...
March 14, 2018: Prostate
Marc A Furrer, Antoni Vilaseca, Renato B Corradi, Silvan Boxler, George N Thalmann, Daniel P Nguyen
BACKGROUND: A growing number of men undergo repeat biopsies prior to radical prostatectomy for prostate cancer. However, the long-term impact of repeat biopsies on functional outcomes in this patient population remains unelucidated. Thus, we compared functional outcomes between patients who underwent single biopsy versus repeat biopsies before radical prostatectomy. METHODS: From 1996 to 2015, 1015 consecutive patients underwent radical prostatectomy, and subsequently had urinary continence and erectile function assessed for >2 years follow-up...
March 14, 2018: Prostate
Stephanie N David, Shanna A Arnold Egloff, Rajen Goyal, Peter E Clark, Sharon Phillips, Lan L Gellert, Omar Hameed, Giovanna A Giannico
BACKGROUND: Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2) promotes the activity of phosphatase and tensin homolog (PTEN). Recent studies suggest that dysregulation of this signaling pathway has a role in prostate carcinogenesis. Our study aims to determine the prognostic significance of MAGI2 expression in prostate cancer. METHODS: Tissue microarrays from 51 radical prostatectomy cases including benign prostatic tissue, high grade prostatic intraepithelial neoplasia (HGPIN), and adenocarcinoma were constructed...
March 14, 2018: Prostate
Shayna E Thomas-Jardin, Mohammed S Kanchwala, Joan Jacob, Sana Merchant, Rachel K Meade, Nagham M Gahnim, Afshan F Nawas, Chao Xing, Nikki A Delk
BACKGROUND: In immunosurveillance, bone-derived immune cells infiltrate the tumor and secrete inflammatory cytokines to destroy cancer cells. However, cancer cells have evolved mechanisms to usurp inflammatory cytokines to promote tumor progression. In particular, the inflammatory cytokine, interleukin-1 (IL-1), is elevated in prostate cancer (PCa) patient tissue and serum, and promotes PCa bone metastasis. IL-1 also represses androgen receptor (AR) accumulation and activity in PCa cells, yet the cells remain viable and tumorigenic; suggesting that IL-1 may also contribute to AR-targeted therapy resistance...
March 11, 2018: Prostate
Neil M Carleton, Guangjing Zhu, Mikhail Gorbounov, M Craig Miller, Kenneth J Pienta, Linda M S Resar, Robert W Veltri
BACKGROUND: There are few tissue-based biomarkers that can accurately predict prostate cancer (PCa) progression and aggressiveness. We sought to evaluate the clinical utility of prostate and breast overexpressed 1 (PBOV1) as a potential PCa biomarker. METHODS: Patient tumor samples were designated by Grade Groups using the 2014 Gleason grading system. Primary radical prostatectomy tumors were obtained from 48 patients and evaluated for PBOV1 levels using Western blot analysis in matched cancer and benign cancer-adjacent regions...
March 9, 2018: Prostate
Marjaana Ojalill, Pekka Rappu, Elina Siljamäki, Pekka Taimen, Peter Boström, Jyrki Heino
BACKGROUND: The composition and organization of extracellular matrix (ECM) are important regulators of cell behavior. In particular in the prostate, this central role of the ECM is further stressed by the fact that several potential markers of prostate stem cells are matrix receptors. METHODS: We established 12 fibroblastic cell lines from cancerous and non-cancerous areas of six prostates and allowed the cells to produce ECM under cell culture conditions. We also performed a proteome wide analysis of the ECM components by mass spectrometry...
March 9, 2018: Prostate
Simon P Keam, Twishi Gulati, Cristina Gamell, Franco Caramia, Cheng Huang, Ralf B Schittenhelm, Oded Kleifeld, Paul J Neeson, Ygal Haupt, Scott G Williams
INTRODUCTION: The development of radioresistance in prostate cancer (PCa) is an important clinical issue and is still largely uninformed by personalized molecular characteristics. The aim of this study was to establish a platform that describes the early oncoproteomic response of human prostate tissue to radiation therapy (RT) using a prospective human tissue cohort. METHODS: Fresh and fixed transperineal biopsies from eight men with clinically localized tumors were taken prior to and 14 days following a single fraction of high-dose-rate brachytherapy...
March 9, 2018: Prostate
Jonathan Hayman, Ryan Phillips, Di Chen, Jamie Perin, Amol K Narang, Janson Trieu, Noura Radwan, Stephen Greco, Curtiland Deville, Todd McNutt, Daniel Y Song, Theodore L DeWeese, Phuoc T Tran
BACKGROUND: Undetectable End of Radiation PSA (EOR-PSA) has been shown to predict improved survival in prostate cancer (PCa). While validating the unfavorable intermediate-risk (UIR) and favorable intermediate-risk (FIR) stratifications among Johns Hopkins PCa patients treated with radiotherapy, we examined whether EOR-PSA could further risk stratify UIR men for survival. METHODS: A total of 302 IR patients were identified in the Johns Hopkins PCa database (178 UIR, 124 FIR)...
March 9, 2018: Prostate
Yishuo Wu, Hongjie Yu, S Lilly Zheng, Rong Na, Mufaddal Mamawala, Tricia Landis, Kathleen Wiley, Jacqueline Petkewicz, Sameep Shah, Zhuqing Shi, Kristian Novakovic, Michael McGuire, Charles B Brendler, Qiang Ding, Brian T Helfand, H Ballentine Carter, Kathleen A Cooney, William B Isaacs, Jianfeng Xu
BACKGROUND: Germline mutations in CHEK2 have been associated with prostate cancer (PCa) risk. Our objective is to examine whether germline pathogenic CHEK2 mutations can differentiate risk of lethal from indolent PCa. METHODS: A case-case study of 703 lethal PCa patients and 1455 patients with low-risk localized PCa of European, African, and Chinese origin was performed. Germline DNA samples from these patients were sequenced for CHEK2. Mutation carrier rates and their association with lethal PCa were analyzed using the Fisher exact test and Kaplan-Meier survival analysis...
March 9, 2018: Prostate
Takatsugu Okegawa, Naoki Ninomiya, Kazuki Masuda, Yu Nakamura, Mitsuhiro Tambo, Kikuo Nutahara
OBJECTIVE: We examined whether androgen receptor splice variant 7 (AR-V7) in circulating tumor cell(CTC)clusters can be used to predict survival in patients with bone metastatic castration resistant-prostate cancer (mCRPC) treated with abiraterone or enzalutamide. METHODS: We retrospectively enrolled 98 patients with CRPC on abiraterone or enzalutamide, and investigated the prognostic value of CTC cluster detection (+ v -) and AR-V7 detection (+ v -) using a CTC cluster detection - based AR-V7 mRNA assay...
March 5, 2018: Prostate
Gabriel H Campolina-Silva, Bruna T Maria, Germán A B Mahecha, Cleida A Oliveira
BACKGROUND: Protective roles have been proposed for vitamin D in prostate cancer, which has the advanced age as the major risk factor. However, little is known about the expression of the vitamin D receptor (VDR) in the aging prostate and its association with the development of epithelial lesions that affect tissue homeostasis and may precede prostate tumors. METHODS: VDR expression in the prostatic complex of young adults to senile Wistar rats, a natural model to study age-related prostatic disorders, was evaluated by immunohistochemical, Western blotting, and image-assisted analyzes...
March 5, 2018: Prostate
Ben T Copeland, Sumanta K Pal, Eric C Bolton, Jeremy O Jones
BACKGROUND: Androgens and the androgen receptor (AR) are necessary for the development, function, and homeostatic growth regulation of the prostate gland. However, once prostate cells are transformed, the AR is necessary for the proliferation and survival of the malignant cells. This change in AR function appears to occur in nearly every prostate cancer. We have termed this the AR malignancy shift. METHODS: In this review, we summarize the current knowledge of the AR malignancy shift, including the DNA-binding patterns that define the shift, the transcriptome changes associated with the shift, the putative drivers of the shift, and its clinical implications...
February 23, 2018: Prostate
Kagenori Ito, Takahiro Kimura, Hajime Onuma, Ryuji Tabata, Tatsuya Shimomura, Kenta Miki, Masayuki Tomita, Shin Egawa
BACKGROUND: Guidelines define docetaxel as a first-line therapeutic option for metastatic castration-resistant prostate cancer (mCRPC). However, the role of docetaxel in non-metastatic castration-resistant prostate cancer (nmCRPC) has not been fully investigated. The aim of this retrospective study was to evaluate the potential role of docetaxel in nmCRPC. Clinical outcomes including overall survival were compared between CRPC patients who had docetaxel introduced while in nonmetastatic versus metastatic diseases...
February 23, 2018: Prostate
Michael A Maccini, Nicholas J Westfall, Adrie Van Bokhoven, Marshall Scott Lucia, Wendy Poage, Paul D Maroni, Shandra S Wilson, Leonard Michael Glodé, Paul Arangua, Jay Newmark, Mitchell Steiner, Priya N Werahera, Elward David Crawford
BACKGROUND: The 4Kscore is a new commercially available blood-based diagnostic test which predicts risk for aggressive, clinically significant prostate cancer on prostate biopsy. The 4Kscore is currently restricted to patients who have not had a digital rectal exam (DRE) in the previous 96 h, owing to prior mixed data suggesting that prostate specific antigen (PSA) isoforms may increase by a statistically significant-if not necessarily clinically significant-amount shortly after DRE...
February 19, 2018: Prostate
Felix Preisser, Marco Bandini, Michele Marchioni, Sebastiano Nazzani, Zhe Tian, Raisa S Pompe, Nicola Fossati, Alberto Briganti, Fred Saad, Shahrokh F Shariat, Hans Heinzer, Hartwig Huland, Markus Graefen, Derya Tilki, Pierre I Karakiewicz
PURPOSE: To assess the effect of pelvic lymph node dissection (PLND) extent on cancer-specific mortality (CSM) in prostate cancer (PCa) patients without lymph node invasion (LNI) treated with radical prostatectomy (RP). METHODS: Within the Surveillance, Epidemiology, and End results (SEER) database (2004-2014), we identified patients with D'Amico intermediate- or high-risk characteristics who underwent RP with PLND, without evidence of LNI. First, multivariable logistic regression models tested for predictors of more extensive PLND, defined as removed lymph node count (NRN) ≥75th percentile...
February 19, 2018: Prostate
Justin Lardizabal, Jun Ding, Zahid Delwar, Paul S Rennie, William Jia
BACKGROUND: Patients with advanced prostate cancer have limited curative options, therefore new treatments are needed. Mouse models play a pivotal role in the discovery and development of new treatments. In the present study, a TRAMP-derived Orthotopic Prostate Syngeneic (TOPS) mouse model was developed and found to provide a consistent means of monitoring tumor and metastatic responses to novel treatments. METHODS: The mouse TOPS model was generated using luciferase transduced TRAMP-C2 prostate cancer cells that were orthotopically injected into Bl6 mice by ultrasound guidance...
February 16, 2018: Prostate
Jiafeng Shou, Qi Zhang, Shuai Wang, Dahong Zhang
BACKGROUND: The present of metastases is a poor prognostic factor in prostate cancer, but the prognostic impact of different distant metastases pattern is unclear. The aim of this study is to investigate the impact of different distant metastases pattern on the survival of patients with stage IV prostate cancer. METHODS: Data queried for this study include prostate cancer (2010-2014) from the Surveillance, Epidemiology, and End Results (SEER) program. Metastatic distribution information was provided for bone, brain, liver and lung...
February 13, 2018: Prostate
Bram De Laere, Steffi Oeyen, Peter Van Oyen, Christophe Ghysel, Jozef Ampe, Piet Ost, Wim Demey, Lucien Hoekx, Dirk Schrijvers, Barbara Brouwers, Willem Lybaert, Els Everaert, Piet Van Kerckhove, Daan De Maeseneer, Michiel Strijbos, Alain Bols, Karen Fransis, Nick Beije, Inge de Kruijff, Valerie van Dam, Anja Brouwer, Pieter-Jan van Dam, Gert Van den Eynden, Annemie Rutten, Stefan Sleijfer, Jean Vandebroek, Steven Van Laere, Luc Dirix
BACKGROUND: The outcome to treatment administered to patients with metastatic castration-resistant prostate cancer (mCRPC) greatly differs between individuals, underlining the need for biomarkers guiding treatment decision making. OBJECTIVE: To investigate the prognostic value of circulating tumor cell (CTC) enumeration and dynamics, in the context of second-line endocrine therapies (ie, abiraterone acetate or enzalutamide), irrespective of prior systemic therapies...
February 12, 2018: Prostate
Xianhan Jiang, Yiqiao Huang, Xue Liang, Funeng Jiang, Yongzhong He, Tian Li, Guibin Xu, Haibo Zhao, Weiqing Yang, Ganggang Jiang, Zhengming Su, Lingke Jiang, Leyuan Liu
BACKGROUND: P62 (also named sequestosome-1, SQSTM1) is involved in autophagy regulation through multiple pathways. It interacts with autophagosomes-associated LC3-II and ubiquitinated protein aggregates to engulf the aggregates in autophagosomes, interacts with HDAC6 to inhibit its deacetylase activity to maintain the levels of acetylated α-tubulin and stabilities of microtubules to enhance autophagosome trafficking, and regulates autophagy initiation and cell survival. We performed immunohistochemistry staining of P62 in prostate tissues from prostate cancer patients and found that levels of P62 in patients with prostate adenocarcinomas (PCA) are significantly higher than those in patients with benign prostate hyperplasia (BPH)...
January 31, 2018: Prostate
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